The "Philadelphia Team" of NTROI investigators is asking fundamental questions with respect to cancer development, lymph node metastases, tumor angiogenesis, and understanding therapeutic response and toxicity of chemotherapy. The Team is developing molecular optical imaging techniques and probes to address these fundamental questions in animal models and is employing technology development, optimization of imaging and independent validation using a variety of imaging techniques including optical imaging. The assembled group of investigators is multidisciplinary and multi-institutional, and includes partners from Industry. The focus and motivating force of this Team are the biological questions driving the required molecular imaging techniques, and this represents a major strength of the consortium. The experimental plan is highly translational with specific goals in mind including early detection of colonic neoplasms, early detection of lymphatic spread, non-invasive imaging of angiogenesis and its correlates hypoxia, hypoglycemia and blood flow, and early detection of specific markers of therapeutic response and toxicity. Efforts are in place to develop imaging of metabolic correlates, to make comparisons with other non-invasive methods, and to develop non-invasive optical imaging methods and probes. There is an effort to develop novel therapeutics to treat polyps, to inhibit angiogenesis and to specifically increase tumor apoptosis using available reagents and compounds as well as through high-throughput chemical library screening using specific molecular imaging algorithms to facilitate the identification of novel and effective agents for cancer therapy. Efforts are in place to develop interactions with industry to bring new technologies or models to the consortium, and efforts are in place to identify and fund projects that are in a Developmental phase. The proposed research directions are likely to have significant impact on the national effort in translational research to develop better methods for early detection, to better predict therapeutic outcome, and to identify novel therapeutic agents and combinations for the treatment of cancer patients.